Lipocortin 1 in apoptosis: mammary regression.

Abstract

Enigmatically, degradation of debris generated in programmed cell death (apoptosis) elicits little inflammation. Having previously detected the upregulation of lipocortin 1 (LC1), a 35-kDa protein with anti-inflammatory and immuno-suppressive properties, at sites of non-inflammatory phagocytosis in the central nervous system (J Neurosci Res 36:491-500, 1993), we sought to determine if LC1 was involved in apoptosis. LC1 immunoreactivity in mammary glands of adult rats was quantified in situ using video microdensitometry before and during postlactational regression. LC1 is present in the mammary ducts but is absent from the alveoli during lactation. One day after weaning, however, LC1 is detected in the lactiferous cells and, as apoptosis proceeds over the ensuing 4 days, total LC1 in the gland increases > 10-fold over resting levels. LC1 remains high in both the apoptotic cells and epithelial phagocytes through day 10, but the total LC1 per gland drops as the apoptotic cells are cleared. Published experiments have shown that LC1 specifically binds Ca++ and phosphatidylserine, and that these affinities are modulated by tyrosine phosphorylation and cross-linking with transglutaminase. Thus, LC1 appears to be a candidate for several putative activities in apoptosis (e.g., phagocyte recognition via phosphatidylserine binding and/or buffering intracellular Ca++) in addition to its anti-inflammatory role.